The Virus Biology Scientific Research Support Component will provide molecular approaches, reagents and service to CHAVI-ID investigators geared toward determining whether T/F viruses have unique biological properties that can be exploited as targets for rational immunogen design. The overall goal is to understand the protective humoral, cellular and innate responses to HIV-1 infection, and to study the structural biology and virology of the T/F virus as a pathogen and immunogen. The Virus Biology Support Component will also explore the impact of Env quasispecies evolution on the development of broadly neutralizing antibodies and characterize human and primate vaccine breakthrough infections to determine whether certain vaccine modalities influence the number, composition, and phenotype of transmitted viruses. Specific Aims Aim 1: Determine whether T/F viruses have common biological properties that comprise favorable targets for vaccine intervention Aim 2: Examine how the evolution of the Env quasispecies contributes to the development of broad neutralizing antibodies Aim 3: Genetically characterize SIV/SHIV challenge stocks and perform sieve analyses of breakthrough infections in actively or passively immunized primates Aim 4: Perform sieve analyses of breakthrough infections in vaccinated humans. These studies will support the B Cell Research Focus as well as Computational, Antibody Sequencing, Structural Biology, Neutralizing Antibodies and NHP SCRCs and will help to find new targets in the HIV-1 transmission pathway that will sharpen the focus of vaccine development efforts.